Structural characterization and immunomodulatory activity of a polysaccharide from Dioscotea opposita.

The purified polysaccharides fraction, DOP-2, was prepared from Dioscorea opposita Thunb (D. opposita). This study combined in vitro and in vivo experiments to comprehensively investigate the index changes in RAW264.7 cells and immunocompromised mice under DOP-2 intervention, aiming to elucidate the potential mechanisms of immunomodulatory effects of DOP-2. DOP-2 (10 âˆ¼ 500 µg/mL) significantly elevated the levels of NO, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) factors secreted by RAW264.7 cells, and restored the body weight of immunosuppressed mice and improve the degree of injury to the immune organ index, resulting in significant immunomodulatory effects. Notably, DOP-2 promoted the production of short-chain fatty acids (SCFAs) in immunosuppressed mice and modulated the composition of their gut microflora. These findings highlight the potential benefits of DOP-2 therapy in improving immune function and gut health, and will provide a theoretical basis for the application of D. opposita polysaccharides as an immunomodulatory adjuvant.

Asymmetric modeling of regional tourism economic disparity in China.

China's tourism economy has experienced significant regional disparities. However, little attention has been paid to understanding the intricate mechanisms through which the interplay of influential factors gives rise to such disparities. Utilizing statistical data from the tourism economy of 31 provinces in mainland China, this study investigates regional tourism economic disparity through the asymmetric modeling of fuzzy set qualitative comparative analysis (fsQCA). The findings reveal that the causes of regional tourism economic disparity exhibit asymmetry; varying approaches contribute to the formation of high and low levels of tourism economy; the functioning of the most influential factors is impacted by other antecedent conditions, presenting an asymmetric non-linear effect; favorable transportation convenience is a necessary condition for a high level of tourism economy, while poor tourism attraction is a necessary condition for a low level of tourism economy. This research not only introduces a fresh perspective on regional tourism economic disparities, enabling an in-depth comprehension of the complex interactions and nonlinear functional mechanisms of influential factors, but also explores a region-based tourism development model, offering valuable practical guidance for policymakers in the tourism sector.

Effects of Extraction Methods on the Physicochemical Properties and Biological Activities of Polysaccharides from Polygonatum sibiricum.

Polygonatum sibiricum polysaccharides (PSPs) have important biological functions, such as antioxidation, immunomodulatory, and hypolipidemic functions. Different extraction methods have effects on their structures and activities. In this study, six extraction methods, including hot water extraction (HWE), alkali extraction (AAE), ultrasound-assisted extraction (UAE), enzyme-assisted extraction (EAE), microwave-assisted extraction (MAE), and freeze-thaw-assisted extraction (FAE) were used to extract PSPs, and their structure-activity relationships were analyzed. The results showed that all six PSPs had similar functional group compositions, thermal stability, and glycosidic bond compositions. PSP-As (PSPs extracted by AAE) exhibited better rheological properties due to their higher molecular weight (Mw). PSP-Es (PSPs extracted by EAE) and PSP-Fs (PSPs extracted by FAE) had better lipid-lowering activity due to their lower Mw. PSP-Es and PSP-Ms (PSPs extracted by MAE), which do not contain uronic acid and have a moderate Mw, had better 1,1-diphenyl-2-picrylhydrazyl (DPPH)-radical-scavenging activity. On the contrary, PSP-Hs (PSPs extracted by HWE) and PSP-Fs, with the Mw of uronic acid, had the best OH-radical-scavenging activity. The high-Mw PSP-As had the best Fe2+-chelating ability. In addition, mannose (Man) may play an important role in the immunomodulatory activity. These results indicate that different extraction methods affect the structure and biological activity of polysaccharides to varying degrees, and these results are helpful for understanding the structure-activity relationship of PSPs.

Structural Characterization, Rheological Properties, Antioxidant and Anti-Inflammatory Activities of Polysaccharides from Zingiber officinale.

The structural characteristics, rheological properties, antioxidant and anti-inflammatory activities of Zingiber officinale polysaccharides (ZOP) and ZOP-1 were studied. The total soluble sugar contents of ZOP and ZOP-1 were 78.6 ± 0.6 and 79.4 ± 0.4%, respectively. Compared with ZOP, ZOP-1 had a larger molecular weight and a more uniform distribution. There were also some differences in the monosaccharide composition between ZOP and ZOP-1. The main monosaccharide of ZOP and ZOP-1 was glucose (Glc) and galactose (Gal), respectively. Ultraviolet visible spectroscopy (UV-Vis) and fourier transform infrared spectra (FT-IR) results showed that the two polysaccharides had the characteristic absorption peaks of polysaccharides and did not contain nucleic acid and protein. They had good thermal stability, trihelix structure and amorphous sheet structure. ZOP and ZOP-1 had obvious differences in microstructure. The surface of ZOP was smooth and the broken structure was compact and stable with angular shape, while the surface of ZOP-1 was uneven with spiral accumulation and not closely arranged. Moreover, ZOP and ZOP-1 were polysaccharides molecular polymers which were entangled by van der waals' force (VDW) between polysaccharides molecules and hydrogen bond association between sugar chains, and both contain α pyranose. At different concentrations, temperature, pH and salt ion concentrations, both ZOP and ZOP-1 had the properties of non-Newtonian fluids, showed shear dilution phenomenon, which had the potential as a texture modifier or thickener in food or biomedicine. Compared with ZOP, ZOP-1 showed superior antioxidant and anti-inflammatory activities in vitro.

Estrogen-induced downregulation of TASK-1 expression through estrogen receptor ß in N2A cells.

BACKGROUND: Our previous data revealed that reduction of TASK-1 expression, as a consequence of exposure to 17ß-estradiol, could participate in neuroprotective effects in N2A cells. However, it is unclear which estrogen receptor underlies these effects of 17ß-estradiol. METHODS AND RESULTS: In this study, the knockdown experiments are carried out to clarify the estrogen receptor responsible for effects of estrogen on TASK-1 channels. Subsequently, data from QPCR measurements reveal that estrogen receptor ß (ERß), but not estrogen receptor α, serves as a binding target for 17ß-estradiol after a 48-h treatment. CONCLUSIONS: The current result suggests the implication of the ERß-dependent manner in the pro-proliferative action of estrogen via TASK-1 channels.

The inhibitory effects of nifedipine on outward voltage-gated potassium currents in mouse neuroblastoma N2A cells.

BACKGROUND: Voltage-gated K(+) (Kv) channels have a pivotal role in tuning the action potential duration and excitability in neuronal cells. Although Ca(2+) channel antagonist nifedipine exhibited an inhibitory effect on cardiac Kv currents, a possible action of nifedipine on neuronal Kv currents has not been fully investigated. METHODS: The effects of nifedipine on elicited Kv currents were characterized using whole-cell recording in mouse neuroblastoma N2A cells. RESULTS: Exposure to nifedipine induced a dose-dependent inhibition of Kv currents with an IC50 value of 22.3±4.2µM and prolonged the time course of activation. The half-maximum activation potential was 1.6±1.7mV in control conditions and became 13.5±1.5mV in 50µM nifedipine. In addition, the decay rate of Kv currents was substantially accelerated by 39.5% at +60mV. For the voltage-dependent inactivation, the half-maximum inactivation potential was -13.8±0.8mV and strongly shifted to the left following treatment with 50µM nifedipine. CONCLUSION: Treatment with nifedipine exerted a strong influence on the activation and inactivation rate of Kv currents as well as an obvious leftward shift in the inactivation curve. These data indicated that nifedipine exerted an inhibitory effect on Kv currents in N2A cells.

The Inhibitory Effects of Ca2+ Channel Blocker Nifedipine on Rat Kv2.1 Potassium Channels.

It is well documented that nifedipine, a commonly used dihydropyridine Ca2+ channel blocker, has also significant interactions with voltage-gated K+ (Kv) channels. But to date, little is known whether nifedipine exerted an action on Kv2.1 channels, a member of the Shab subfamily with slow inactivation. In the present study, we explored the effects of nifedipine on rat Kv2.1 channels expressed in HEK293 cells. Data from whole-cell recording showed that nifedipine substantially reduced Kv2.1 currents with the IC50 value of 37.5 ± 5.7 µM and delayed the time course of activation without effects on the activation curve. Moreover, this drug also significantly shortened the duration of inactivation and deactivation of Kv2.1 currents in a voltage-dependent manner. Interestingly, the half-maximum inactivation potential (V1/2) of Kv2.1 currents was -11.4 ± 0.9 mV in control and became -38.5 ± 0.4 mV after application of 50 µM nifedipine. The large hyperpolarizing shift (27 mV) of the inactivation curve has not been reported previously and may result in more inactivation for outward delayed rectifier K+ currents mediated by Kv2.1 channels at repolarization phases. The Y380R mutant significantly increased the binding affinity of nifedipine to Kv2.1 channels, suggesting an interaction of nifedipine with the outer mouth region of this channel. The data present here will be helpful to understand the diverse effects exerted by nifedipine on various Kv channels.

17ß-Estradiol Upregulated Expression of α and ß Subunits of Larger-Conductance Calcium-Activated K(+) Channels (BK) via Estrogen Receptor ß.

Large-conductance Ca(2+)-activated K(+) channels, which were known as BK channels, were widely distributed in brain tissues and played a crucial role in neuroprotection. Previous studies found that estrogen, a steroid hormone, was able to interact with distinct K(+) channels such as Kv (voltage-gated K(+) channels) in various tissues. However, current knowledge about possible effects of estrogen on BK channels is rather poor. In the present study here, the investigation for the interaction of estrogen with BK channels was performed in mouse N2A cells and human SK-N-SH cells. At first, the different expression patterns of α and ß subunits of BK channels in these cells were explored by conducting RT-PCR. After exposure to varying dose of 17ß-estradiol (E2) for 24 h, the messenger RNA (mRNA) levels of these BK channel subunits in both N2A and SK-N-SH cells were significantly increased in a concentration-dependent way. A prolonged incubation for 48 h also potentiated the effects of E2 on ß1 and ß4 subunits in N2A cells as well as α and ß3 subunits in SK-N-SH cells. The small interfering RNAs (siRNAs) against the ERα (siERα) or ERß (siERß) was induced into N2A and SK-N-SH cells by transfection and resulted in a decrease in the level of corresponding ER transcript. Furthermore, treatment with siERß but not siERα attenuated the action of E2 on BK channel subunits, suggesting that estradiol exerted its action by binding to ERß. Our data indicated that 17ß-estradiol was able to regulate the expression of BK channel subunits via ERß.